1gua
From Proteopedia
(New page: 200px<br /> <applet load="1gua" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gua, resolution 2.0Å" /> '''HUMAN RAP1A, RESIDUE...) |
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| - | [[Image:1gua.gif|left|200px]]<br /> | + | [[Image:1gua.gif|left|200px]]<br /><applet load="1gua" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1gua" size=" | + | |
caption="1gua, resolution 2.0Å" /> | caption="1gua, resolution 2.0Å" /> | ||
'''HUMAN RAP1A, RESIDUES 1-167, DOUBLE MUTANT (E30D,K31E) COMPLEXED WITH GPPNHP AND THE RAS-BINDING-DOMAIN OF HUMAN C-RAF1, RESIDUES 51-131'''<br /> | '''HUMAN RAP1A, RESIDUES 1-167, DOUBLE MUTANT (E30D,K31E) COMPLEXED WITH GPPNHP AND THE RAS-BINDING-DOMAIN OF HUMAN C-RAF1, RESIDUES 51-131'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Members of the Ras subfamily of small GTP-binding proteins have been shown | + | Members of the Ras subfamily of small GTP-binding proteins have been shown to be promiscuous towards a variety of putative effector molecules such as the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange factor (Ral-GEF). To address the question of specificity of interactions we have introduced the mutations E30D and K31E into Rap and show biochemically, by X-ray structure analysis and by transfection in vivo that the identical core effector region of Ras and Rap (residues 32-40) is responsible for molecular recognition, but that residues outside this region are responsible for the specificity of the interaction. The major determinant for the switch in specificity is the opposite charge of residue 31--Lys in Rap, Glu in Ras--which creates a favourable complementary interface for the Ras-Raf interaction. |
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: LEOPARD syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164760 164760]], Noonan syndrome 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164760 164760]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 1GUA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, CA and GNP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1GUA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GUA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: oncogene protein/kinase/effector protein gtp-binding-protein]] | [[Category: oncogene protein/kinase/effector protein gtp-binding-protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:54:05 2008'' |
Revision as of 10:54, 21 February 2008
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HUMAN RAP1A, RESIDUES 1-167, DOUBLE MUTANT (E30D,K31E) COMPLEXED WITH GPPNHP AND THE RAS-BINDING-DOMAIN OF HUMAN C-RAF1, RESIDUES 51-131
Contents |
Overview
Members of the Ras subfamily of small GTP-binding proteins have been shown to be promiscuous towards a variety of putative effector molecules such as the protein kinase c-Raf and the Ral-specific guanine nucleotide exchange factor (Ral-GEF). To address the question of specificity of interactions we have introduced the mutations E30D and K31E into Rap and show biochemically, by X-ray structure analysis and by transfection in vivo that the identical core effector region of Ras and Rap (residues 32-40) is responsible for molecular recognition, but that residues outside this region are responsible for the specificity of the interaction. The major determinant for the switch in specificity is the opposite charge of residue 31--Lys in Rap, Glu in Ras--which creates a favourable complementary interface for the Ras-Raf interaction.
Disease
Known diseases associated with this structure: LEOPARD syndrome 2 OMIM:[164760], Noonan syndrome 5 OMIM:[164760]
About this Structure
1GUA is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Ras/Rap effector specificity determined by charge reversal., Nassar N, Horn G, Herrmann C, Block C, Janknecht R, Wittinghofer A, Nat Struct Biol. 1996 Aug;3(8):723-9. PMID:8756332
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